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Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice
Core 1- and core 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We foun...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097036/ https://www.ncbi.nlm.nih.gov/pubmed/27143302 http://dx.doi.org/10.1038/mi.2016.45 |
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author | Bergstrom, Kirk Fu, Jianxin Johansson, Malin EV Liu, Xiaowei Gao, Nan Wu, Qian Song, Jianhua McDaniel, J Michael McGee, Samuel Chen, Weichang Braun, Jonathan Hansson, Gunnar C Xia, Lijun |
author_facet | Bergstrom, Kirk Fu, Jianxin Johansson, Malin EV Liu, Xiaowei Gao, Nan Wu, Qian Song, Jianhua McDaniel, J Michael McGee, Samuel Chen, Weichang Braun, Jonathan Hansson, Gunnar C Xia, Lijun |
author_sort | Bergstrom, Kirk |
collection | PubMed |
description | Core 1- and core 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(−/−)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and core 3-derived O-glycans (DKO) developed spontaneous colitis in both distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(−/−) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than WT mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients. |
format | Online Article Text |
id | pubmed-5097036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-50970362017-02-01 Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice Bergstrom, Kirk Fu, Jianxin Johansson, Malin EV Liu, Xiaowei Gao, Nan Wu, Qian Song, Jianhua McDaniel, J Michael McGee, Samuel Chen, Weichang Braun, Jonathan Hansson, Gunnar C Xia, Lijun Mucosal Immunol Article Core 1- and core 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(−/−)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and core 3-derived O-glycans (DKO) developed spontaneous colitis in both distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(−/−) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than WT mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients. 2016-05-04 2017-01 /pmc/articles/PMC5097036/ /pubmed/27143302 http://dx.doi.org/10.1038/mi.2016.45 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Bergstrom, Kirk Fu, Jianxin Johansson, Malin EV Liu, Xiaowei Gao, Nan Wu, Qian Song, Jianhua McDaniel, J Michael McGee, Samuel Chen, Weichang Braun, Jonathan Hansson, Gunnar C Xia, Lijun Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title | Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title_full | Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title_fullStr | Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title_full_unstemmed | Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title_short | Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
title_sort | core 1- and core 3-derived o-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097036/ https://www.ncbi.nlm.nih.gov/pubmed/27143302 http://dx.doi.org/10.1038/mi.2016.45 |
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